The secret business of not-so-legal highs

A quick Google search of ‘legal highs’ brings up many results of legal high sellers. By clicking on one of these links you are thrown into the depths of the legal high industry in a firework-esque website page with vibrant colours and imaginative names; not dissimilar to a Year 7’s Bebo page.

So why are legal-highs, well…legal? The fact is that the composition of drugs changes so rapidly that it is extremely difficult to illegalise every component and combination as quickly as they are being made. Legal highs (the typical example being of plant food) are also usually marked ‘not for human consumption’ allowing them to still be sold for their primary purpose. Just as sniffing glue or Tipp-Ex may give you a solvent abuse high.
Manufacturers of legal highs may search a compound library or old literature from the pharmaceutical industry, in the hope of finding an active scaffold structure. This part is called the pharmacophore. Active compounds are often cited in past drug discovery papers where a drug was developed that was too potent or caused hallucinogenic, stimulant or euphoric side effects. Therefore they could not to be used as a medicinal drug.

These are starting points for making potent legal highs. Once a pharmacophore is found, substituents can be added to tweak the psychoactive nature of the drug for desired effect. These side groups may cause an enhanced binding to neuroreceptors in the brain. Imagine a receptor being the lock and the drug being the key, the better the key fits the lock, the greater the effect. Once a pharmacophore is found, a range of analogues are produced with side chains to optimise activity. The manufacturer often then tests the drugs on themselves to review the desired effect.

MDMA is a common starting scaffold. The pharmacophore mimics the serotonin neurotransmitter structure generating the effects of feeling close to others and euphoria. MDMA binds to the serotonin receptors on the post-synaptic neuron and increases the amount of serotonin in the brain by increasing its release and inhibiting its removal. This creates continuous impulses through the brain.

Adding certain functional groups to this pharmacophore, tweaks the mimicry of the drug to bind better to the serotonin receptor to achieve a better and longer lasting high. Adding substituents can also make it more easily administered. For instance, MDMA crystals are swallowed or rubbed on the gums; by adding hydrophilic groups to ecstasy the solubility is increased for easier and quicker metabolism and release of the active compound.
The main concern of legal highs presently is cannabinoid analogues, most infamously, ‘spice’. This family of drugs all bind to the cannabinoid receptor mimicking the effects of THC – the active compound in cannabis.

Previous users of Class A drugs have reported that weening off heroin is easier than coming off spice which causes horrific withdrawal symptoms.

A ‘psychoactive substances bill’ in Ireland bans any psychoactive substance intended for human consumption, with the exceptions of alcohol, caffeine, tobacco, food and medical products. This also includes the use and sale of nitrous oxide or ‘laughing gas’, made popular in clubs abroad. Under this ban, producers and sellers of legal highs could be sentenced to up to seven years in jail. Planned to be enforced in the UK from 6 April, it has been postponed indefinitely as a review of the Irish blanket ban has shown a decrease in hospital admittance due to legal highs, but an increase in usage. This creates great concern as users who need desperate help may avoid hospital for life-saving treatment and long-term addicts may avoid seeking help as they are afraid of the judicial consequences.

The great concern with legal highs is the buyers don’t know what they are getting. Most of the drugs are new on the market, and minimal if any have been properly tested for human use. If people are going to take these substances, I believe they will whether they are legal or not. The great issue comes when users don’t have a safe place to go if things go wrong.